Prostaglandins (PGs) are organic carboxylic acids, namely cyclopentanes carrying two side chain substituents, typically linear C6-C8 side chains, bonded to adjacent positions on the cyclopentane nucleus. One of the side chains, the α-side chain, carries a terminal carboxylic acid group. Many are natural products found in mammalian organs and tissues (primary PGs), and exhibit a variety of physiological activities. Primary PGs generally have a prostanoic acid skeleton, which forms the basis of the nomenclature:α

A significant number of synthetic PG analogs have been made and found to have useful pharmacological properties. These may have modified skeletons, and substituted and unsaturated side chains. PGs are characterized by a hydroxyl (or ketone) substituent on the cyclopentane nucleus, position 9.
Prostaglandin analogs are difficult to synthesize. Complications arise because of the requirements of the end products to have several functional groups and two side chains of significant size and complexity. Stereospecificity is commonly required, for substituent groups and for bonds in the core. Since the products are intended for pharmaceutical use, the range of industrially acceptable reagents, solvents, catalysts, etc. which can be used in their synthesis is limited to those having pharmaceutical industry acceptability.
A common starting material for PG analog synthesis is the commercially available Corey alcohol benzoate, of formula:

To convert this to a synthetic PG analog, many protection, functionalization, de-protection, etc. steps are required to form the desired side chains. U.S. Pat. No. 5,252,605 Ueno, issued Oct. 12, 1993, reports several PG syntheses starting from Corey alcohol which involve approximately fifteen steps. Inevitably, such a multi-step process is time consuming and expensive to conduct, and results in relatively low overall yield of final product.
An example of a synthetic prostaglandin analog of specific interest is lubiprostone, reported to be a solid crystalline compound of formula:
but also, at least in solution, having a mono-cyclic structural isomeric form of formula:
the two isomeric compounds being inter-convertible so that both forms are present in admixture in solution.
Lubiprostone is marketed as “Amitiza”, for use in treatment of chronic idiopathic constipation, irritable bowel syndrome and post-operative ileus.
The synthesis of lubiprostone presents significant technical challenge because of the chemical complexity of the fluorine containing substituent chain at the 12-position. Known methods for its synthesis suffer from the aforementioned disadvantages, namely a multi-step (typically 15-step) synthesis from Corey alcohol with consequent low yields of final product and time consuming nature of the process.
It is an object of the present invention to provide a novel synthetic method for preparing PG analogs, in fewer steps and in improved overall yield.
It is a further object to provide novel chemical compounds useful in the synthesis of PG analogs.
It is a specific object of the present invention to provide a novel synthesis of lubiprostone, starting from commercially available Corey alcohol, and novel forms and compositions of lubiprostone.